EVALUATION OF BETA CELL FUNCTION IN NEWLY DIAGNOSED TYPE 2 DIABETES MELLITUS IN CLINICAL PRACTICE
Abstract
Dysfunctions underlining type 2 diabetes mellitus (DM2) evolution are insulin resistance and beta-cell secretory insufficiency. Practical but reliable beta-cell function (BCF) testing is still elusive. Methods of BCF measurement include the homeostasis model assessment (HOMA), glucagon stimulation test (GST), oral glucose tolerance tests (OGTT), intravenous glucose tolerance tests (IVGTT), meal tolerance tests (MTT) and the hyperglycemic clamp procedure. Oral tests have the advantage of simpler use and superior approximation of real-life stimulation inclusive for incretin activation effects. The advantage of the test meal over the OGTT incudes a more adequate simulation of nutrients effect on incretin secretion. Therefore, a standardized test meal (STO) would best reflect the spike in insulin secretion after a meal in real life.
Conclusion: Standardized test meal, as potent stimulus of C-peptide secretion, is a promising simple and naturalistic alternative to in vivo assess beta-cell function in an affordable outpatient setting, through analysis of C-peptide response in newly diagnosed diabetic patients, as potent stimulus of C-peptide secretion.
References
1. Sun H, Saeedi P, Karuranga S, Pinkepank M , Ogurtsova K , Duncan B et al. IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res Clin Pract. 2022 Jan;183:109119.
2. Ferrannini E, Mari A.β-Cell function in type2 diabetes.Metabolism.2014 Oct;63(10):1217-27.
3. Kahn SE, Chen YC, Esser N, Taylor AJ, van Raalte DH, Zraika S et al. The β Cell in Diabetes: Integrating Biomarkers With Functional Measures.Endocr Rev. 2021 Sep 28;42(5):528-583.
4. Holst JJ. From the Incretin Concept and the Discovery of GLP-1 to Today's Diabetes Therapy.Front Endocrinol (Lausanne). 2019 Apr 26;10:260.
5. Rehfeld JF. The Origin and Understanding of the Incretin Concept.Front Endocrinol (Lausanne). 2018 Jul 16;9:387.
6. Drucker DJ. Mechanisms of Action and Therapeutic Application of Glucagon-like Peptide-1.Cell Metab. 2018 Apr 3; 27(4):740-756.
7. Nauck MA, Vardarli I, Deacon CF, Holst JJ, Meier JJ. Secretion od glucagons like peptide-1 (GLP-1)in type 2 diabetes: what’s up, what’s down? Diabetologia. 2011;54:10-18.
8. Chia CW, Odetunde JO, Kim W, Carlson OD, Ferrucci L, Egan JM. GIP contribtesto islet tri-hormonal abnormalities in type 2 diabetes. J Clin Endocrinol Metab 2014; 99:247-85.
9. Kramer CK, Zinman B, Retnakaran R. Short-term intensive insulin therapy in type 2 diabetes mellitus: a systematic review and meta-analysis. Lancet Diabetes Endocrinol. 2013 Sep;1(1):28-34.
10. Kahn SE, Zraika S, Utzschneider KM, Hull RL.The beta cell lesion in type 2 diabetes: there has to be a primary functional abnormality. Diabetologia. 2009 Jun;52(6):1003-12.
11. Mahajan A, Wessel J, Willems SM, Zhao W, Robertson NR, Chu AY et al. Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes. Nat Genet. 2018 Apr;50(4):559-571.
12. Yuval D, Glaser B. Beta-Cell Dedifferentiation and Type 2 Diabetes.The New England Joural of Medicine 2013; 368:572-573.
13. Retnakaran R. Novel Strategies for Inducing Glycemic Remission during the Honeymoon Phase of Type 2 Diabetes. Canadian Journal od Diabetes. 2015; 39:142-147.
14. Knudsen JG, Rorsman P. β Cell Dysfunction in Type 2 Diabetes: Drained of Energy? Cell Metab. 2019 Jan 8;29(1):1-2.
15. Liu L, Liu J, Xu L, Ke W, Wan X, Li H et al. Lower mean blood glucose during short-term intensive insulin therapy is associated with long-term glycemic remission in patients with newly diagnosed type 2 diabetes: Evidence-based recommendations for standardization. J Diabetes Investig. 2018 Jul;9(4):908-916.
16. Rahier J, Guiot Y, Goebbels RM, Sempoux C, Henquin JC. Pancreatic Beta cell mass in Europian subjects with type 2 diabetes. Diabetes Obes Metab 2008;10(suppl 4):32-42.
17. Cersosimo E, Solis-Herrera C, Trautmann ME, Malloy J, Triplitt CL.
Assessment of pancreatic β-cell function: review of methods and clinical applications.
Curr Diabetes Rev. 2014 Jan;10(1):2-42.
18. DeFronzo RA, Tobin JD, Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance.Am J Physiol. 1979 Sep;237(3):E214-23.
19. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC.
Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985 Jul;28(7):412-9.
20. Wallace TM, Levy JC, Matthews DR. Use and abuse of HOMA modeling.Diabetes Care. 2004 Jun;27(6):1487-95.
21. Leighton E, Sainsbury CA, Jones GC. A Practical Review of C-Peptide Testing in Diabetes.
Diabetes Ther. 2017 Jun;8(3):475-487.
22. Escobar-Jiménez F, Herrera Pombo JL, Gómez-Villalba R et al. A standard breakfast test: an alternative to glucagon testing for C-peptide reserve? Horm Metab Res. 1990;22(6):339-41.
23. Greenbaum CJ, Mandrup-Poulsen T, McGee PF, Battelino T, Haastert B, Ludvigsson J et al. Type 1 Diabetes Trial Net Research Group; European C-Peptide Trial Study Group. Mixed-meal tolerance test versus glucagon stimulation test for the assessment of beta-cell function in therapeutic trials in type 1 diabetes. Diabetes Care. 2008 Oct;31(10):1966-71.
24. Fujioka Y, Okura T, Sumi K, Matsumoto K, Shoji K, Nakamura R et al. Normal meal tolerance test is preferable to the glucagon stimulation test in patients with type 2 diabetes that are not in a hyperglycemic state: Comparison with the change of C-peptide immunoreactivity.J Diabetes Investig. 2018;9(2):274-278
25. Marena S, Montegrosso G, De Michieli F, Pisu E, Pagano G. Comparison of the metabolic effects of mixed meal and standard oral glucose tolerance test on glucose, insulin and C-peptide response in healty, impaired glucose tolerance, mild and severe non-insulin-dependent diabetic subjects.Acta Diabetol. 1992;29(1):29-33.
26. Wopereis S, Stroeve JHM, Stafleu A, Bakker GCM, Burggraaf J, van Erk MJ et al. Multi-parameter comparison of a standardized mixed meal tolerance test in healthy and type 2 diabetic subjects: the PhenFlex challenge. Genes Nutr. 2017; 12:21.
27. Pozzan R, Dimetz T, Gazzola HM, Gomes MB. Dicriminative capacity of fasting C-peptide levels in a functional test according to different criteria of response to a stimulus. A study of Brazilian insulin dependent diabetic patients. Acta Diabetolog.1997;34(1):42-45.
28. Prando R, Odetti P, Melga P, Giusti R, Ciuchi E, Cheli V. Progressive deterioration of beta-cell function in nonobese type 2 diabetic subjects. Postprandial plasma C-peptide level is an indication of insulin dependency. Diabetes Metab. 1996;22(3):185-91.
29. Stumvoll M, Mitrakou A, Pimenta W, Jenssen T, Yki-Järvinen H, Van Haeften T et al. Use of the oral glucose tolerance test to assess insulin release and insulin sensitivity.Diabetes Care. 2000 Mar;23(3):295-301.
30. Koprivica B, Beljić-Živković T, ILLe T. Značaj test–obroka u proceni uvođenja insulina u lečenje dijabetes melitusa tip2. Srpski Arh Celok Lek. 2009;137(9-10):490-49.
31. Jones AG, Hattersley AT. The clinical utility of C-peptide measurement in the care of patients with diabetes. Diabet Med. 2013;30(7):803-17.
32. Saisho Y. Postprandial C-Peptide to Glucose Ratio as a Marker of β Cell Function: Implication for the Management of Type 2 Diabetes.Int J Mol Sci. 2016 May 17;17(5):744.
33. Rossetti L, Giaccari A, DeFronzo RA. Glucose toxicity. Diabetes Care 1990; 13: 610–630.
34. Funakoshi S, Fujimoto S, Hamasaki A, Fujiwara H, Fujita Y, Ikeda K et al. Analysis of factors influencing postprandial C‐peptide levels in Japanese patients with type 2 diabetes: comparison with C‐peptide levels after glucagon load. J Diabetes Investig. 2011; 2: 429–434.
35. Beljić Živković T. Terapijski priručnik za dijabetes tip 2: Sekrecija insulina. Beograd: Medicinski fakultet Univerziteta u Beogradu; 2019. str.31-34.
36. Ahren B,Pratley RE, Soubt M, Dunning BE, Foley JE: Clinical measures of islet function: usefulness to characterize defects in diabetes. Curr Diab Rev 2008;4:129-145.
37. Bonnet-Serrano F, Abou Jaoude M, Laguillier C, Gobeaux C, Bouzerara A, Mosnier-Pudar H et al. Pattern of C-peptide response to oral glucose tolerance test: Interest and cut-off values. Ann Endocrinol (Paris). 2022 Apr;83(2):95-102.
38. Okuno Y, Komada H, Sakaguchi K, Nakamura T, Hashimoto N, Hirota Y et al. Postprandial serum C-peptide to plasma glucose concentration ratio correlates with oral glucose tolerance test-and glucose clamp-based disposition indexes. Metabolism.2013 Oct;62(10):1470-6.
39. Oberhauser L, Jiménez-Sánchez C, Madsen JGS, Duhamel D, Mandrup S, Brun T et al. Glucolipotoxicity promotes the capacity of the glycerolipid/NEFA cycle supporting the secretory response of pancreatic beta cells. Diabetologia. 2022 Apr;65(4):705-720.
40. Carroll JF, Kaiser KA, Franks SF, Deere C, Caffrey JL. Influence of BMI and gender on postprandial hormone responses.Obesity (Silver Spring). 2007 Dec;15(12):2974-83.
41. Leone A, De Amicis R, Bertoli S, Spadafranca A, De Carlo G, Battezzati A. Absence of a sexual dimorphism in postprandial glucose metabolism after administration of a balanced mixed meal in healthy young volunteers. Nutr Diabetes. 2022 Feb 2;12(1):6.
42. Mari A, Schmitz O, Gastaldelli A, Oestergaard T, Nyholm B, Ferrannini E. Meal and oral glucose tests for assessment of beta-cell function: modeling analysis in normal subjects. Am J Physiol Endocrinol Metab 2002; 283: E1159-66.
43. Sasaki H, Saisho Y, Inaishi J, Itoh H. Revisiting Regulators of Human β-cell Mass to Achieve β-cell-centric Approach Toward Type 2 Diabetes. J Endocr Soc. 2021 Jul 19;5(10):bvab128.
44. Davies MJ, D'Alessio DA, Fradkin J, Kernan WN, Mathieu C, Mingrone G et al. Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2018 Dec;41(12):2669-2701.
45. Ahlqvist E, Storm P, Käräjämäki A, Martinell M, Dorkhan M, Carlsson A et al. Novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables. Lancet Diabetes Endocrinol. 2018;6(5):361-369.
46. Abdelgani S, Puckett C, Adams J, Triplitt C, DeFronzo RA, Abdul-Ghani M.
Insulin Secretion Predicts the Response to Antidiabetic Therapy in Patients With New-onset Diabetes.J Clin Endocrinol Metab. 2021 Nov 19;106(12):3497-3504.
47. DeFronzo RA. Banting Lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus.Diabetes. 2009 Apr;58(4):773-95.